Adaptive trial designs: a review of barriers and opportunities

Trials

Keith E Muller³  Mitchell A Thomann²  Christopher S Coffey²  John A Kairalla¹ 

[1]Department of Biostatistics, University of Florida, PO Box 117450, Gainesville, FL, 32611-7450, USA

[2]Department of Biostatistics, University of Iowa, 2400 University Capitol Centre, Iowa City, IA, 52240-4034, USA

[3]Department of Health Outcomes and Policy, University of Florida, PO Box 100177, Gainesville, FL, 32610-0177, USA

关键词: Small clinical trials;    Comparative effectiveness research;    Sample size re-estimation;    Power;    Internal pilot;    Group sequential;    Flexible designs;    Adaptive designs;   

Others  :  1095385
DOI  :  10.1186/1745-6215-13-145

 received in 2012-02-16, accepted in 2012-08-08,  发布年份 2012

【 摘 要 】

Adaptive designs allow planned modifications based on data accumulating within a study. The promise of greater flexibility and efficiency stimulates increasing interest in adaptive designs from clinical, academic, and regulatory parties. When adaptive designs are used properly, efficiencies can include a smaller sample size, a more efficient treatment development process, and an increased chance of correctly answering the clinical question of interest. However, improper adaptations can lead to biased studies. A broad definition of adaptive designs allows for countless variations, which creates confusion as to the statistical validity and practical feasibility of many designs. Determining properties of a particular adaptive design requires careful consideration of the scientific context and statistical assumptions. We first review several adaptive designs that garner the most current interest. We focus on the design principles and research issues that lead to particular designs being appealing or unappealing in particular applications. We separately discuss exploratory and confirmatory stage designs in order to account for the differences in regulatory concerns. We include adaptive seamless designs, which combine stages in a unified approach. We also highlight a number of applied areas, such as comparative effectiveness research, that would benefit from the use of adaptive designs. Finally, we describe a number of current barriers and provide initial suggestions for overcoming them in order to promote wider use of appropriate adaptive designs. Given the breadth of the coverage all mathematical and most implementation details are omitted for the sake of brevity. However, the interested reader will find that we provide current references to focused reviews and original theoretical sources which lead to details of the current state of the art in theory and practice.

【 授权许可】

   
2012 Kairalla et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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