Therapeutic concepts

Abstract

Combinations of different medicinal products are widely use in the medical practice and are in fact essential for the treatment of several diseases. The existing regulation for approval of medicinal products offers only a remote possibility for the approval of combination therapies. Usually, active agents are evaluated in terms of their individual safety and efficacy. For exceptional cases, guidelines and regulations exist for the approval of specific combinations, such as fixed combinations, which includes two or more active agents within a single pharmaceutical form. The free combination of individual medications or other medical products is however currently not reflected in the legal framework, meaning a gap between treatment reality and regulatory process exists. A possible approach for closing this gap is the introduction of “therapeutic concepts” which is presented in this thesis. <br /> Therapeutic concepts describe the marketing authorisation of a treatment regime consisting of a combination of two or more individual medicinal products for a defined condition or a combination of a medicinal product and a companion device that is compulsory for diagnosis or decision-making, that have been developed and studied together. Therapeutic concepts can be regarded as an integrative approach based on the current framework. The approach would be an addition to the present legislation to meet existing needs. Compared to fixed combinations the free combination of a therapeutic concept would offer additional benefits, such as better dosage adjustment based on the individual patient’s need. <br /> At present, combinations of medicinal products in certain conditions are for example described in medical guidelines. However, medical guidelines differ greatly in quality from each other, having the status of recommendation and cannot be equated with a market authorisation. Defined regulations for a market authorisation of combinations based on evidence obtained from clinical studies provide a greater knowledge and control on combinations in use and an improved legal certainty compared to medical guidelines. <br /> Combinations of different medicinal products have been commonly used as treatment systems, often in complex or multifactorial diseases, such as bacterial infection (e.g. tuberculosis), cardiovascular diseases or cancer. Current research focuses now on genetics-associated diseases, which also often require a complex combination of diagnostics and medicine. This field of research is referred to as personalized medicine. The patient’s individual disease and metabolic markers are analysed to stratify patients into subgroups which receive a therapy based on their genetic profile that is more likely to be effective compared to an alternative medication. Due to the complexity of the treatment approach and the involvement of both medicinal products and diagnostics, the field of personalized medicine would profit from approved therapeutic concepts and would be a possible area for the application of therapeutic concepts. The link between medicinal products and medical devices, which are actually subject to different regulations, can be strengthened by therapeutic concepts. <br /> For a possible implementation of therapeutic concepts as a new regulatory approval pathway, several aspects have to be considered. The design of pivotal studies for the approval process should allow as much evidence on safety and effectiveness as possible without too many control arms in the study as this might be too time and cost-consuming and requires a high number of participants. Labelling, reimbursement and risk management are particularly challenging for therapeutic concepts. Labelling must be designed in such a way that the individual medicinal product can be identified as part of an approved therapeutic concept. Risk management und vigilance plans should be more extensive to reflect to additional risk caused by the combination.