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

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.SS’s work was funded by the European Union's FP7 programme grant number 602552 for the IDEAL project