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. 2010 Aug;42(4):201-7.
doi: 10.4103/0253-7613.68417.

Adaptive design clinical trials: Methodology, challenges and prospect

Rajiv Mahajan  1 , Kapil Gupta
Affiliations

Adaptive design clinical trials: Methodology, challenges and prospect

Rajiv Mahajan et al. Indian J Pharmacol. 2010 Aug.

Abstract

New drug development is a time-consuming and expensive process. Recently, there has been stagnation in the development of novel compounds. Moreover, the attrition rate in clinical research is also on the rise. Fearing more stagnation, the Food and Drug Administration released the critical path initiative in 2004 and critical path opportunity list in 2006 thus highlighting the need of advancing innovative trial designs. One of the innovations suggested was the adaptive designed clinical trials, a method promoting introduction of pre-specified modifications in the design or statistical procedures of an on-going trial depending on the data generated from the concerned trial thus making a trial more flexible. The adaptive design trials are proposed to boost clinical research by cutting on the cost and time factor. Although the concept of adaptive designed clinical trials is round-the-corner for the last 40 years, there is still lack of uniformity and understanding on this issue. This review highlights important adaptive designed methodologies besides covering the regulatory positions on this issue.

Keywords: Adaptation; clinical trials; innovations; statistical analysis.

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Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Drop-the-loser design (with intervening response-adaptive randomization)
Figure 2
Figure 2
Adaptive seamless phase II/III design (2a) and its comparison with classical Phase II and III trials (2b)
Figure 3
Figure 3
A multiple adaptive design (combining response-adaptive randomization, drop-the-loser design and seamless phase II/III design)[10]
See this image and copyright information in PMC

References

    1. Woodcock J. FDA introduction comments: Clinical studies design and evaluation issues. Clin Trials. 2005;2:273–5. - PubMed
    1. Innovation or Stagnation: Challenge and opportunity on the critical path to new medical products. Washington DC, USA: Food and Drug Administration; 2004. Food and Drug Administration. Available from: http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html [cited on 2010 Apr 30]
    1. Mucke HA, editor. Adaptive Clinical Trials: Innovations in Trial Design, Management and Analysis. Needham, USA: Cambridge Healthtech Institute; 2007. CHI Insight Pharma Reports- Adaptive trials in current practice survey- May 2007.
    1. Woodcock J, Woosley R. The FDA critical path initiative and its influence on new drug development. Annu Rev Med. 2008;59:1–12. - PubMed
    1. Innovation or Stagnation: Critical Path Opportunities List. Washington DC, USA: Food and Drug Administration; 2006. Food and Drug Administration. Available from: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathI... [cited on 2010 Apr 30]