Statistical issues in first-in-human studies on BIA 10-2474: Neglected comparison of protocol against practice.

  • Competence Center for Methodology and Statistics
March 01, 2017 By:
  • Bird SM
  • Bailey RA
  • Grieve AP
  • Senn S.

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.

2017 Mar. Pharm Stat.16(2):100-106. Epub 2017 Feb 16.
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