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Statistical issues in first‐in‐human studies on BIA 10‐2474: Neglected comparison of protocol against practice
Author(s) -
Bird Sheila M.,
Bailey Rosemary A.,
Grieve Andrew P.,
Senn Stephen
Publication year - 2017
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1801
Subject(s) - protocol (science) , dosing , suite , protocol design , medicine , computer science , operations research , pharmacology , political science , engineering , alternative medicine , law , operating system , pathology , communications protocol
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.