ArticleBritish journal of clinical pharmacology2017
Pharmacological vs. classical approaches in the design of first in man clinical drug trials.
Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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
2 citing papers in PubMed.
- Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.BMC medicine · 2023Review
- Pharmacological vs. classical approaches in the design of first in man clinical drug trials.British journal of clinical pharmacology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe aims of the present study were to investigate the role of pharmacology in the design of first-in-man (FIM) trials in the Netherlands, and to evaluate the change in design approaches between 2007 and 2015.
methodsAll FIM drug trials approved by all Dutch Institutional Review Boards (IRBs) in 2007 and in 2015 were selected. The original trial protocols, investigator's brochures and investigational medicinal product dossiers were the data sources. The following four design elements were assessed on the justification of the chosen approaches: preclinical information, dose calculation, endpoints, and dose escalation.
resultsIn 2007, the Dutch IRBs approved 21 FIM trials, and in 2015 they approved 34 FIM trials (55 in total). Seven out of 21 (33%) of the FIM trials from 2007, and 14 out of the 34 (41%) FIM trials from 2015 discussed only the no-observed-adverse-effect level or no-observed-effect level as preclinical information. Furthermore, five of the 21 (24%) 2007 FIM trials and 12 of the 34 (35%) 2015 FIM trials used unexplained allometric scaling. Pharmacodynamic (PD) parameters were measured in 15 of the 21 (71%) 2007 FIM trials and in 31 of the 34 (91%) of the 2015 FIM trials, and allometric scaling was only guided by safety/tolerability in 11 of the 20 (55%) dose escalation trials in 2007 and in nine of the 33 (27%) dose escalation trials in 2015.
conclusionsTrial protocols and investigator's brochures commonly lack pharmacokinetic/PD approaches. Investigators, sponsors and IRBs should require an upfront consideration of pharmacology in these aspects for all FIM trials.
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