Point and Interval Estimation of Primary and Secondary Parameters in a Two-Stage Adaptive Clinical Trial

Abstract

Investigated in this paper is the point estimation and confidence intervals of the treatment efficacy parameter and related secondary parameters in a two-stage adaptive trial. Based on the minimal sufficient statistics, several alternative estimators to the sample averages are proposed to reduce the bias and to improve the precision of estimation. Confidence intervals are constructed using Woodroofe's pivot method. Numerical studies are conducted to evaluate the bias and mean squared error of the estimators and the coverage probability of the confidence intervals.

Key Words:

• Adaptive design
• Bias
• Confidence intervals
• Effect size
• Mean squared error
• Minimal sufficiency
• Pivot function
• Sample size reestimation

ACKNOWLEDGMENTS

Research of the authors was fully supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. The opinions expressed in the article are not necessarily of the National Institutes of Health. The authors thank two referees for their valuable comments that helped improve the manuscript.

Notes

LBEP: probability of lower confidence bound exceeding the parameter.

UBEP: probability of upper confidence bound exceeding the parameter.

CP: probability of confidence interval containing the parameter.

LBER: probability of lower confidence bound exceeding the parameter.

UBEP: probability of upper confidence bound exceeding the parameter.

CP: probability of confidence interval containing the parameter.