Statistical issues in first-in-human studies on BIA 10-2474: Neglected comparison of protocol against practice
Accepted version
Peer-reviewed
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Repository DOI
Change log
Authors
Bird, S
Bailey, RA
Grieve, AP
Senn, S
Abstract
By setting the regulatory-approved protocol for a suite of first-in-human studies on BIA 10-2474 against the subsequent French investigations, we highlight six key design and statistical issues which reinforce recommendations by a Royal Statistical Society Working Party which were made in the aftermath of cytokine release storm in six healthy volunteers in the UK in 2006. The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies.
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Keywords
combined approvals, first-in-human, healthy volunteer, protocol, recommendations, study design
Journal Title
Pharmaceutical Statistics
Conference Name
Journal ISSN
1539-1604
1539-1612
1539-1612
Volume Title
16
Publisher
Wiley
Publisher DOI
Sponsorship
SS’s work was funded by the European Union's FP7 programme grant number 602552 for the IDEAL project.