Benefits, challenges and obstacles of adaptive clinical trial designs

Orphanet Journal of Rare Diseases

Ralph Corey²  Shein-Chung Chow¹ 

[1] Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA;Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA

关键词: Two-stage seamless adaptive design;    Adaptive dose finding;    Group sequential design;    Less well-understood design;    Well-understood design;    Efficiency;    Flexibility;   

Others  :  864488
DOI  :  10.1186/1750-1172-6-79

 received in 2011-08-22, accepted in 2011-11-30,  发布年份 2011

【 摘 要 】

In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.

【 授权许可】

   
2011 Chow and Corey; licensee BioMed Central Ltd.

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