Adaptive design in clinical research: issues, opportunities, and recommendations.
The issues and opportunities of adaptive designs are discussed. Starting with the definitions of an adaptive design, its validity and integrity are discussed. The three key components of an adaptive design, i.e., Type I error control, p-value adjustment, and unbiased estimation and confidence interval are addressed. Various seamless designs are investigated. Recommendations are made in the following aspects: study planning, trial monitoring, analysis and reporting, trial simulation, and regulatory perspectives.
Chang
Mark
M
Millennium Pharmaceuticals Inc, Cambridge, MA 02139, USA. mark.chang@statisticians.org
Chow
Shein-Chung
SC
Pong
Annpey
A
D001499:Bayes Theorem; D002986:Clinical Trials as Topic / Q000191:economics / Q000379:methods*; D003627:Data Interpretation, Statistical; D017408:Guidelines as Topic; D006801:Humans; D012107:Research Design; D018401:Sample Size