AMNOG – Erste Erfahrungen und mögliche Auswirkungen auf die Klinische Forschung

Background and Objective

On January 1st 2012 the German Law for Reforming the Market for Pharmaceuticals (Arzneimittelverordnungsgesetz: AMNOG) came into force. This law stipulated an early benefit assessment for new drugs for the first time. The acknowledgement of an additional benefit compared to the standard of care is a precondition for price negotiations with payers. 13 Pharmaceutical companies, launching a new agent in 2011, provided 19 benefit assessment dossiers to the Federal Joint Committee. The German Scientific Association for Market Access (DFGMA) decided to execute an expert survey as early as possible. The aim of the expert survey was to explore experiences during the compilation of the early benefit dossier, the implication of the law on clinical research and the requirements for the benefit assessment process.

Method

10 experts, directly involved in the production of the early benefit dossier, from 9 pharmaceutical companies reported in telephone interviews of about 60 minute duration on their experiences, and discussed possible implications.

Results

The most important issues are: (a) the appropriate comparator set forth by the G-BA (Gemeinsamer Bundesausschuss), (b) post-hoc groupings of subgroups and subgroup analyses and, (c) exclusion of surrogate parameters. The criteria for the selection of the appropriate comparator are not clearly defined. Without clinical trials with the required comparator it seems to be nearly impossible to get a positive benefit assessment. Post-hoc subgroup analyses are critical for methodological reasons, because for unplanned subgroups the numbers for statistical analyses are inadequate and the results are lacking appropriate confidence levels. The exclusion of surrogate parameters also dilutes the results of clinical trials.

Conclusion

The requirements of the early benefit assessment in Germany should be considered in the very early phases of the development of a new drug. For pipeline candidates in phase I a sound analysis of reimbursement and market access issues should be performed. Phase II should include a much broader investigation than nowadays of the potential of the new agent, i.e. searching for patient groups with higher risk or special benefits, proof of concept studies optionally with several comparators and the assessment of appropriate patient relevant endpoints. Phase III trials must aim for superiority at least for a specified patient group.

With regard to the benefit assessment process, improved coordination and unification of the requirements for the regulatory and reimbursement authorities seem to be desirable. The requirements should be clear, pragmatic and feasible to ensure medical innovations in Germany.