Artikel
Population Sizes and Methodological Quality of Clinical Trials in the Era of “Personalized Medicine”: An Analysis of more than 100 Early Benefit Assessments of New Drugs in Germany 2011-2015
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Autoren
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Dirk Eyding
- MDS e.V., Essen, Deutschland
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Daniela Preukschat
- MDS e.V., Essen, Deutschland
| Veröffentlicht: | 23. Februar 2016 |
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Gliederung
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Introduction: Highest possible level of evidence in the era of “personalized medicine” is claimed to be increasingly difficult to generate due to ever smaller populations in the increasing number of (sub-)indications. Regulatory bodies respond to this with ideas like adaptive licensing where the requirement for well conducted RCTs to get approval may be softened or even eliminated.
Since 2011 all drugs entering the German market have to undergo an Early Benefit Assessment (EBA) where the added benefit against an appropriate comparator is determined within 6 months after market entry. At the day of market entry the drug company has to submit a dossier containing the claim of an added benefit and its justification and also an estimation of the 12 month prevalence of the approved indication in Germany. Due to its early timepoint after approval the clinical trials documented in the dossier are mostly the same ones as used for getting regulatory approval.
Objective: To describe the relation between the methodological quality of clinical trials in EBAs and the epidemiologically estimated population sizes for drugs new on the German market between 2011 and 2015.
Methods: All EBAs since start were analyzed based on the published documents on the Federal Joint Committee’s (GBA) Website (https://www.g-ba.de/). Relevant methodological aspects were extracted. Main aspect was trial design, i.e. RCT(s) vs. Non-RCT(s). Additionally, the size of the trial(s), the comparator, the risk of bias, the status as orphan drug (vs. non-orphan) and the data on 12 month prevalence in Germany were extracted.
At a descriptive level the relation between aspects of the clinical trials and the size of the respective population was analyzed, differentiated by the orphan status. Some cases at the lower end of population sizes were analyzed qualitatively in more detail.
Results: Across all EBAs there was a weak positive correlation between trial size and population size (based on the 12 month prevalence as reported in the EBA) – for orphans as well as for non-orphans. Trial sizes as well as population sizes were smaller for orphans than for non-orphans. RCT-evidence was generated for populations as small as estimated 10 German patients per year.
Conclusion: RCT-evidence is possible to generate even in small populations.
