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

Sheila M. Bird; Rosemary A. Bailey; Andrew P. Grieve; Stephen Senn

doi:10.1002/pst.1801

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

Sheila M. Bird^*, Rosemary A. Bailey, Andrew P. Grieve, Stephen Senn

^*Corresponding author for this work

Research output: Contribution to journal › Comment/debate

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	100-106
Number of pages	7
Journal	Pharmaceutical Statistics
Volume	16
Issue number	2
DOIs	https://doi.org/10.1002/pst.1801
Publication status	Published - 1 Mar 2017

Keywords

combined approvals
first-in-human
healthy volunteer
protocol
recommendations
study design

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10.1002/pst.1801

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

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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author = "Bird, \{Sheila M.\} and Bailey, \{Rosemary A.\} and Grieve, \{Andrew P.\} and Stephen Senn",

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T2 - Neglected comparison of protocol against practice

AU - Bird, Sheila M.

AU - Bailey, Rosemary A.

AU - Grieve, Andrew P.

AU - Senn, Stephen

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - combined approvals

KW - first-in-human

KW - healthy volunteer

KW - protocol

KW - recommendations

KW - study design

UR - https://www.scopus.com/pages/publications/85013302167

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M3 - Comment/debate

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JO - Pharmaceutical Statistics

JF - Pharmaceutical Statistics

IS - 2

ER -

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

Abstract

Keywords

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