Off-Label-Therapie: aktuelle Probleme aus Sicht der Arzneimittelkommission der deutschen Ärzteschaft

Abstract

The off-label use of approved pharmaceuticals outside the authorized status is implemented in pharmacotherapy of many diseases, especially for rare diseases and in cases of therapy resistance. The German regulations are presented and analyzed and the relative literature is discussed.

Off-Label Use in Rare Diseases: Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenic Syndromes

“…Numerous guidelines of the Association of the Scientific Medical Societies (AWMF) describe substances used off-label as well as the related level of evidence and assessment. Off-label use may be required for the physician if these guidelines have clearly formulated the conditions for the drug treatment, and the off-label use meets the requirements of the various opinions of the Federal Social Court or relevant opinions of the Federal Constitutional Court [3][4][5][6] or if no on-label therapy is available for the disease [7]. An assumption of costs by the German statutory health insurance (GKV) can in principle only be made if a substantiating application is made by the treating neurologist before the beginning of the therapy as well as a positive opinion of the health insurance medical service (MDK) and/or prior consent of the GKV is available.…”

“…The extent of the off-label use thus obtained in accordance within the process or outside standard procedure ("tolerated" off-label use) has not been systematically investigated in Germany. With regard to liability, it should be noted that a manufacturer who is aware of widespread off-label use of a product must be held liable in accordance with Section 84 of the German Drug Law [3].…”

“…The prerequisites for improving the evidence for new substance approval for a rare disease have previously been elaborate, presum-ably not very attractive to a pharmaceutical manufacturer to undertake classical random clinical trials, e. g., to expand the current authorization. In its "Rapid Report", the German Institute for Quality and Efficiency in Healthcare (IQWiG) indicated that the methodological procedure regarding rare diseases is practically the same as for non-rare diseases [3]. However, even with the concept of a rare disease there are "singular cases" [10] or "individual cases", which are considered "ultra-rare diseases" (prevalence: < 1:10,000), including, for example MuSK-positive myasthenia gravis (prevalence 0.05-0.65/100,000 [10]) or congenital myasthenic syndrome (CMS) [20].…”

“…Substances in Part A can be prescribed directly without prior request by the GKV and costs assumed by the GKV, if the guidelines specified in the G-BA decision are adhered to, which are more or less an extension of the tech-nical information. Treatment with MMF and IVIg that can be ordered and costs assumed by the GKV is a positive result of this procedure, but requires special instruction and monitoring ( [3,4]; ▶ table 2).…”

Neue Arzneimittel in der Onkologie: Merkmale klinischer Zulassungsstudien und Argumente für die rasche Durchführung unabhängiger klinischer Studien nach der Zulassung

“…In der Hämatologie und Onkologie werden neue Arzneimittel zunehmend häufig als OD zugelassen - mehr als 50% der in den letzten 10 Jahren von der EMA zugelassenen 64 OD betreffen hämatologische oder onkologische Indikationen [22] - und anschließend, auch aufgrund der eng definierten Anwendungsgebiete, häufig außerhalb der Zulassung (off label) eingesetzt [20,21,22,23,24]. …”