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,Volker E Amelung,Jörg Ruof,Georg Isbary

doi:10.1186/s12913-016-1902-8

Thomas Staab, Volker E Amelung + Show 2 more

Open Access

https://doi.org/10.1186/s12913-016-1902-8

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Abstract

BackgroundPrevious 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.MethodsMedicines 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.ResultsA 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1902-8) contains supplementary material, which is available to authorized users.

Highlights

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)
The pharmaceutical manufacturer (PM) needs to submit an EBA dossier evaluating the additional benefit of the drug, based on available clinical trial data, to the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA)
Analysis of patient relevance of primary endpoints in the benefit assessment by the G-BA: The resulting dataset was used to analyse whether PEPs used in the clinical studies and reported in the PM dossiers went on to be accepted as patient-relevant in the G-BA appraisals

Summary

Introduction

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 patientrelevant 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. The pharmaceutical manufacturer (PM) needs to submit an EBA dossier evaluating the additional benefit of the drug, based on available clinical trial data, to the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA). The opinion of the G-BA on patient relevance of endpoints frequently diverges from those of regulatory authorities [4,5,6,7,8]

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