Recent advances in methodology for clinical trials in small populations: the InSPiRe project

被引：33

作者：

Friede, Tim ^{[1
]}

Posch, Martin ^{[2
]}

Zohar, Sarah ^{[3
]}

Alberti, Corinne ^{[4
]}

Benda, Norbert ^{[5
]}

Comets, Emmanuelle ^{[6
,7
]}

Day, Simon ^{[8
]}

Dmitrienko, Alex ^{[9
]}

Graf, Alexandra ^{[2
]}

Guenhan, Burak Kuersad ^{[1
]}

Hee, Siew Wan ^{[10
]}

Lentz, Frederike ^{[5
]}

Madan, Jason ^{[10
]}

Miller, Frank ^{[11
]}

Ondra, Thomas ^{[2
]}

Pearce, Michael ^{[12
]}

Roever, Christian ^{[1
]}

Toumazi, Artemis ^{[1
]}

Unkel, Steffen ^{[1
]}

Ursino, Moreno ^{[3
]}

Wassmer, Gernot ^{[2
]}

Stallard, Nigel ^{[10
]}

机构：

[1] UMG, Gottingen, Germany

[2] Med Univ Vienna, Sect Med Stat, CeMSIIS, Vienna, Austria

[3] Univ Paris 06, Univ Paris 05, Ctr Rech Cordeliers, INSERM,U1138,Team 22, Paris, France

[4] Univ Paris 07, Hop Robert Debre, APHP, INSERM, Paris, France

[5] BfArM, Bonn, Germany

[6] Univ Paris Diderot, Sorbonne Paris Cite, INSERM, IAME,UMR 1137, Paris, France

[7] Univ Rennes 1, INSERM, CIC 1414, Rennes, France

[8] Clin Trials Consulting & Training Ltd, Buckingham, England

[9] Mediana Inc, Overland Pk, KS USA

[10] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

[11] Stockholm Univ, Dept Stat, Stockholm, Sweden

[12] Univ Warwick, Complex Sci, Coventry, W Midlands, England

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2018年 / 13卷

关键词：

FP7 small populations methodology projects; Statistical methods; Rare disease clinical trial; DECISION-THEORETIC DESIGNS; ADAPTIVE DESIGNS; SAMPLE-SIZE; METAANALYSIS; INFORMATION;

D O I：

10.1186/s13023-018-0919-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods.

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页数：9

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