ArticleBritish journal of clinical pharmacology2019
Body of evidence and approaches applied in the clinical development programme of fixed-dose combinations in the European Union from 2010 to 2016.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effectiveness of Single-Tablet Combination Therapy in Improving Adherence and Persistence and the Relation to Clinical and Economic Outcomes.Journal of health economics and outcomes research · 2024Pooled it
- Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia-Approved Products and Challenges.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Demonstrating Contribution of Components of Fixed-Dose Drug Combinations Through Longitudinal Exposure-Response Analysis.The AAPS journal · 2020Article
- Body of evidence and approaches applied in the clinical development programme of fixed-dose combinations in the European Union from 2010 to 2016.British journal of clinical pharmacology · 2019Article
- Optimizing Dose-Finding Studies for Drug Combinations Based on Exposure-Response Models.The AAPS journal · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo provide insights into the clinical development pathway for fixed-dose combinations (FDCs), to consider strategies, and to elucidate the path to approval by assessing the body of evidence, as summarized in the European Public Assessment Reports.
methodsThe main resource was the European Public Assessment Reports for 36 FDCs, which included 239 clinical trials with 157 514 patients. The analyses focused on how prior knowledge of the active substances or combination, use of pharmacokinetic-pharmacodynamic modelling, and clinical trial design choice impact the size and strategy of the clinical development programme.
resultsFDC products primarily comprised 2 previously approved components (21/36, 71%) and had only 1 approved combination (21/36, 71%). Utilizing previously approved active substances resulted in fewer clinical trials, arms and patients, but FDC doses studied in the clinical development programme. Furthermore, dose-finding trials were performed for less than half of FDCs consisting of 2 previously approved active substances. The standard approach to demonstrate contribution of active substances was through a factorial or single combination study. Finally, the use of pharmacokinetic modelling showed a significant decrease in the number of FDC doses studied.
conclusionsThe field of FDCs seems to be on the rise, utilizing new molecular entities, prior knowledge and re-profiling drugs. However, a way to move FDC development forward might be through new regulatory and scientific paradigms, in which it is encouraged to utilize model-based approaches to develop FDCs with multiple dose levels and dose ratios for exposure-based treatment that will enable personalization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.