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. 2016 Nov 14;16(1):651.
doi: 10.1186/s12913-016-1902-8.

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

Thomas Staab  1 , Georg Isbary  1 , Volker E Amelung  2 , Jörg Ruof  3   4
Affiliations

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

Thomas Staab et al. BMC Health Serv Res. .

Abstract

Background: Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas.

Methods: Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer's dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed.

Results: A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas.

Conclusions: This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany.

Keywords: AMNOG; Early benefit assessment; HTA; Marketing authorisation; Morbidity; Primary endpoint.

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Figures

Fig. 1
Fig. 1
Patient relevance of PEPs according to the G-BA by endpoint dimension. a All three therapeutic areas, b oncological diseases, c metabolic diseases, and d infectious diseases. HRQoL was not used as PEP for any assessment, therefore it is not shown in the graphs
Fig. 2
Fig. 2
Adaptable and disease-specific weighting of endpoint categories
See this image and copyright information in PMC

References

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