Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The Relevance of the Label in the Context of the Early Benefit Assessment (EBA) of Medicinal Products: a Systematic Quantification of the Deviations of Marketing Authorization Labels Compared to the Underlying Pivotal Studies and the Consequences for the Extent of Added Benefit

Dr. Markus Molitor (Abschlußjahr: 2018)

Summary
Language: English
In 2011 the AMNOG was introduced to the German market for medicinal products in order to improve the quality and at the same time limit the expenditures in the healthcare sector. After proving its quality, safety and efficacy and receiving the marketing authorization, the added benefit of medicinal products now has to be assessed in the EBA. Due to the different objectives, both procedures differ in their specific requirements.
The final decision concerning the added benefit is made by the G-BA, the underlying scientific assessment may be forwarded to the IQWiG.
The result of the EBA is the basis for the following price negotiations, which will lead to the price for which the medicinal product will be sold on the German market. The result of this process may therefore be an important factor for the success of a new medicinal product. This in mind it is important to understand in which cases and why an added benefit was not granted in the past in order to be successful in the EBA in the future.
This thesis gives an overview about the reasons of failure in the EBA, by analyzing the G-BA decisions between the beginning of the EBA in 2011 and the end of 2017, with special attention to the deviations of marketing authorization labels compared to the underlying pivotal studies. The reasons for failure in the EBA were extracted from G-BA decisions on the level of subgroups and were then collected in different categories.
This thesis shows that reasons of failure from all examined groups of categories were relevant, this included reasons concerning the implementation of the intervention and the ACT, reasons concerning indirect comparisons and reasons concerning the study design and operationalization of endpoints. By far the most important category were reasons concerning the deviations of the marketing authorization labels compared to the underlying pivotal studies: In many cases the pivotal study population did not cover the whole marketing authorization label. Thus, in the separate evaluation of subgroups by the G-BA, for many subgroups there was no evidence available, with consequently no added benefit being granted.
Also it was found that subgroups failed in the EBA due to evidence that covered a larger population than the population of the respective subgroup.
The collected frequencies of failure reasons show that all examined groups of categories were relevant. Thus ways to avoid potential reasons of failure should be explored in all these areas.
The pharmaceutical entrepreneur may increase the rate of success, by considering the specific requirements of the German EBA procedure and the German market. These should be considered at an early stage, already during the design of the pivotal studies.
Also it is crucial to represent all subgroups relevant for the marketing of the medicinal product in the study population of the pivotal studies. These subgroups should exactly match the subgroups which will later be analyzed by the G-BA and IQWiG in order to present applicable evidence.
The authorities, particularly the G-BA, may further clarify their specific guidances concerning in particular the choice of the ACT, the methods of indirect comparisons and the operationalization of patient-relevant endpoints. It might also be considered to allow the transfer of best-available evidence to subgroups that were not covered by the pivotal trial.
Also a better alignment with the requirements and methods used in the marketing authorization procedure may facilitate successful EBAs.
A suitable means of exchange between the pharmaceutical entrepreneur and the G-BA is the existing possibility of advisory meetings. These should however, in order to have an impact on the pivotal study design, including the subgroups, the ACT and the endpoints, take place at an early stage before or during the design of the pivotal studies.
Pages: 44