ASTIN: a Bayesian adaptive dose-response trial in acute stroke

被引:52
作者
Grieve, AP [1 ]
Krams, M
机构
[1] Pfizer Global Res & Dev, Stat Res & Consulting Ctr, Sandwich CT13 9NJ, Kent, England
[2] Pfizer Inc, Clin CNS, Groton, CT 06340 USA
关键词
D O I
10.1191/1740774505cn094oa
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Understanding the dose-response is critical for successful drug development. We describe an adaptive design to efficiently learn about the dose-response and the ED(95). A dynamic termination rule allows for early discontinuation either for efficacy or futility. The design was deployed in ASTIN, a phase II proof-of-concept trial of the neuroprotectant, neutrophil inhibitory factor (NIF), in acute stroke. We discuss the learning from this trial.
引用
收藏
页码:340 / 351
页数:12
相关论文
共 9 条
[1]  
Berry D.A., 2002, Case Studies in Bayesian Statistics, V5, P99
[2]   OUTCOME AND TIME-COURSE OF RECOVERY IN STROKE .1. OUTCOME - THE COPENHAGEN STROKE STUDY [J].
JORGENSEN, HS ;
NAKAYAMA, H ;
RAASCHOU, HO ;
VIVELARSEN, J ;
STOIER, M ;
OLSEN, TS .
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION, 1995, 76 (05) :399-405
[3]   Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) - An adaptive dose-response study of UK-279,276 in acute ischemic stroke [J].
Krams, M ;
Lees, KR ;
Hacke, W ;
Grieve, AP ;
Orgogozo, JM ;
Ford, GA .
STROKE, 2003, 34 (11) :2543-2548
[4]   UK-279,276, a neutrophil inhibitory glycoprotein, in acute stroke - Tolerability and pharmacokinetics [J].
Lees, KR ;
Diener, HC ;
Asplund, K ;
Krams, M .
STROKE, 2003, 34 (07) :1704-1709
[5]   Optimizing the science of drug development: Opportunities for better candidate selection and accelerated evaluation in humans [J].
Lesko, LJ ;
Rowland, M ;
Peck, CC ;
Blaschke, TF .
JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 40 (08) :803-814
[6]   CHOICE OF NUMBER OF DOSES FOR MAXIMUM-LIKELIHOOD-ESTIMATION OF THE ED50 FOR QUANTAL DOSE-RESPONSE DATA [J].
MULLER, HG ;
SCHMITT, T .
BIOMETRICS, 1990, 46 (01) :117-129
[7]   Learning versus confirming in clinical drug development [J].
Sheiner, LB .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1997, 61 (03) :275-291
[8]  
TAMURA RN, J AM STAT ASS, V89, P768
[9]  
West M., 2006, Bayesian forecasting and dynamic models