[Risk-benefit evaluation of medicinal products. An element of Health Technology Assessment]

This paper aims to further develop and specify the method and the process of risk-benefit evaluation for determining the safety of medicinal products in national and European pharmaceutical law. The term "safety" (Unbedenklichkeit=the relationship between efficacy and harmfulness) is one of the central categories of national and European pharmaceutical law. The guaranteeing of the safety of pharmaceuticals is not a static but a dynamic and process oriented objective. It aims to preserve what has been approved on the one hand, and to increase the standard of safety by innovation on the other. A medicinal product is only found to be safe if the result of the risk-benefit evaluation is a positive risk-benefit balance. Safety must be guaranteed permanently through the entire lifecycle of the medicinal product. One must differentiate between absolute safety, which is related to the individual product, and relative safety, which is related to already available medicinal products of the same indication. The process of risk-benefit evaluation is determined by the indication of the medicinal product. The different types of medicinal products or their different mechanisms of action require different risk-benefit evaluations. The established, estimated and evaluated benefit has to be compared with the established, estimated and evaluated risks of the medicinal product. The comparative risk-benefit evaluation requires a procedural optimisation of benefits as well as minimisation of risks and a reciprocal optimisation of both requirements. If the comparison of the benefits and risks of the product results in a negative risk-benefit balance, the product is rated absolutely unsafe. The product is relatively unsafe if its standard of safety is lower than that of already available pharmaceuticals of the same indication and the existing safety gap (increased benefit or lesser risks) is deemed considerable. Differences in benefit and/or differences in risk between the medicinal products compared in the risk/benefit evaluation render the assessment more difficult and require differentiation. Such differentiation, based on indication, has to be appropriate from the doctor's perspective and desirable from the perspective of the patient. Both perspectives have to be considered in the risk/benefit evaluation under the aspect of risk acceptance ("justifiable").