Statistical issues in first‐in‐human studies on BIA 10‐2474: Neglected comparison of protocol against practice |
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| Authors: | Sheila M Bird Rosemary A Bailey Andrew P Grieve Stephen Senn |
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| Institution: | 1. MRC Biostatistics Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK;2. School of Mathematics and Statistics, University of St Andrews, St Andrews, UK;3. ICON plc, Marlow, UK;4. Competence Center for Methodology and Statistics, Luxembourg Institute of Health, Strassen, Luxembourg |
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| 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 6 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 6 healthy volunteers in the United Kingdom 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 |
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